History

The hallmark feature of rheumatoid arthritis (RA) is persistent symmetric polyarthritis (synovitis) that affects the hands and feet, although any joint lined by a synovial membrane may be involved. The severity of RA may fluctuate over time, but chronic RA most commonly results in the progressive development of various degrees of joint destruction, deformity, and a significant decline in functional status. Extra-articular involvement of organs such as the skin, heart, lungs, and eyes can also be significant.

Juvenile idiopathic arthritis (JIA), sometimes referred to as juvenile rheumatoid arthritis (JRA), is the most common form of childhood arthritis. In most patients, the immunogenic associations, clinical pattern, and functional outcome of JIA are different from those of adult-onset RA.

Patients with RA may report difficulty performing activities of daily living (ADLs), such as dressing, standing, walking, personal hygiene, or use of their hands. In addition to articular deterioration, constitutional symptoms (eg, fatigue, malaise, morning stiffness, weight loss, and low-grade fever) may be present.

In most patients, RA has an insidious onset. It may begin with systemic features (eg, fever, malaise, arthralgias, and weakness) before the appearance of overt joint inflammation and swelling. A small percentage (approximately 10%) of patients with this disease have an abrupt onset with the acute development of synovitis and extra-articular manifestations. Spontaneous remission is uncommon, especially after the first 3-6 months.

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Physical Examination

During the physical examination, it is important to assess the following:

Stiffness

Tenderness

Pain on motion

Swelling

Deformity

Limitation of motion

Extra-articular manifestations

Rheumatoid nodules

Joint involvement is the characteristic feature of RA. In general, the small joints of the hands and feet are affected in a relatively symmetric distribution. In decreasing frequency, the metacarpophalangeal (MCP), wrist, proximal interphalangeal (PIP), knee, metatarsophalangeal (MTP), shoulder, ankle, cervical spine, hip, elbow, and temporomandibular joints are most commonly affected.

Affected joints show inflammation with swelling, tenderness, warmth, and decreased range of motion (ROM). Atrophy of the interosseous muscles of the hands is a typical early finding. Joint and tendon destruction may lead to deformities such as ulnar deviation, boutonniere and swan-neck deformities, hammer toes, and, occasionally, joint ankylosis.

Other commonly observed musculoskeletal manifestations include the following:

Tenosynovitis (defined as inflammation of the tendon and its enveloping tendon sheath) and associated tendon rupture due to tendon and ligament involvement, most commonly involving the fourth and fifth digital extensor tendons at the wrist

This deformity occurs as a result of synovitis stretching or rupturing the PIP joint through the central extensor tendon, with concomitant volar displacement of the lateral bands. When the lateral bands have subluxed far enough to pass the transverse axis of the joint, they become flexors of the PIP joint. Hyperextension of the DIP joint occurs as the tendons shorten with time. A compensatory and reducible hyperextension may occur at the MCP joint. Consequences of boutonniere deformity are loss of thumb mobility and pincher grasp.

Swan-neck deformity of the finger describes hyperextension at the PIP joint with flexion of the DIP joint (see the image below).

This deformity may be initiated either (a) by disruption of the extensor tendon at the DIP joint, with secondary shortening of the central extensor tendon and hyperextension of the PIP joint, or (b) by volar herniation of the PIP joint capsule due to weakening from chronic synovitis, with subsequent tightening of the lateral bands and central extensor tendon. The lateral bands may become shortened over time and lie dorsally, limiting PIP flexion and ineffectively extending the DIP joint.

Tightness of intrinsic muscles (eg, the interossei and lumbricals) may cause major declines in finger mobility. This tightness is ascertained on examination when the PIP joint cannot be flexed while the MCP joint is fully extended but can be flexed while the MCP is in flexion (Bunnell test); primary PIP joint pathology is evident with the MCP joint in either position. For accurate assessment, the phalanx must be aligned with the metacarpal; when ulnar deviation at the MCP joint exists, the intrinsic muscles on the ulnar side are slack, allowing more motion.

Flexor tenosynovitis of the fingers is common and suggests a poor prognosis. “Triggering” of the finger occurs when thickening or nodule formation of the tendon interacts with the concomitant tenosynovial proliferation, trapping the tendon in a flexed position (stenosing tenosynovitis). Tendon rupture may occur as a consequence of infiltrative synovitis in the digit or bony erosion of the tendon at the wrist (especially the flexor pollicis longus).

Arthritis mutilans (sometimes called opera glass hands) results if destruction is severe and extensive, with dissolution of bone. In the small joints of the hands, the phalanges may shorten, and the joints may become grossly unstable. Pulling on the fingers during examination may lengthen the digit in a manner resembling the opening of opera glasses, or the joint may bend in unusual directions merely under the pull of gravity.

Metacarpophalangeal joints

Two typical deformities that alter the alignment of the palmar skeletal arches and the stability of the fingers may occur at the MCP joints: volar subluxation and ulnar deviation (see the image below).

Subluxation in the metacarpophalangeal joints, with ulnar deviation, in a patient with rheumatoid arthritis of the hands.

Most cases of ulnar deviation are accompanied by counterpoised radial deviation of the wrist, roughly proportional to the degree of ulnar deviation of the fingers. The volar plate is firmer and more substantial than other portions of the MCP joint capsule, thus effectively limiting extension and dorsal movement at the joint. The greater strength of the flexor muscles relative to the extensor muscles causes volar migration of the proximal phalanx after synovial-based inflammation has weakened ligament and tendon insertions about the MCP joint capsule.

Ulnar deviation occurs after synovitis has led to stretching and attenuation of the volar plate and collateral ligaments, allowing dislocation of the flexor tendon volarward and ulnarward. The supporting structures of the extensor tendons also may become attenuated or destroyed by synovial distention and invasion, loosening the tendons so that they no longer ride centrally and dorsally over the metacarpal head but move into the cleft between the MCP joints.

If the extensor tendon subluxation is beyond the transverse axis of the MCP joint, the tendon becomes a flexor at that joint, further limiting the active extension of the fingers.

Wrists

Multiple deformities may occur in the wrist. Disruption of the radioulnar joint with dorsal subluxation of the ulna (caput ulnae) as well as rotation of the carpus on the distal radius with an ulnarly translocated lunate are common. The combination of an ulnar drift of the fingers and carpal rotation is known as a zigzag deformity. Shortening of the carpal height (noted on radiographs), due in part to cartilage loss, is seen with rotational deformities.

Dorsal subluxation of the ulna often allows the ulnar styloid to be depressed volarly on examination, much as a piano key is depressed when played. It may lead to rupture of the extensor tendons of the little, ring, and long fingers because the end of the distal ulna is roughened secondary to erosion of bone and may abrade the tendons as they move during normal hand function, much as a rope is frayed when rubbed over a sharp rock (see the image below). This process is especially likely to lead to tendon rupture if tenosynovitis is present.

Coronal, T1-weighted magnetic resonance imaging scan shows characteristic pannus and erosive changes in the wrist in a patient with active rheumatoid arthritis. Courtesy of J. Tehranzadeh, MD, University of California at Irvine.

Entrapment neuropathy may result from synovitis about the flexor tendons. Entrapment of the median nerve as it passes through the carpal tunnel leads to decreased sensation on the palmar aspect of the thumb, index finger, and long finger and on the radial aspect of the ring finger; weakness and atrophy of the muscles in the thenar eminence also occurs. Entrapment of the ulnar nerve at the wrist, a less frequent event, causes decreased sensation over the little finger and the ulnar aspect of the ring finger and decreased interosseous muscle strength and mass.

Elbow

Elbow involvement is often detected by palpable synovial proliferation at the radiohumeral joint and is commonly accompanied by a flexion deformity, such as in contractures. Involvement of the olecranon bursa is common, as are rheumatoid nodules in the bursa and along the extensor surface of the ulna (see the image below).

Rheumatoid nodules at the elbow. Photograph by David Effron MD, FACEP.

RA commonly involves the shoulders and is manifested by tenderness, nocturnal pain, and limited motion. Initially, swelling occurs anteriorly, but it may be difficult to detect and is present on examination in a minority of patients at any point in time.

Rotator cuff degeneration secondary to synovitis may limit abduction and rotation. Superolateral migration of the humerus occurs with complete tears. Glenohumeral damage results in pain with motion and at rest and typically leads to severely restricted motion or “frozen shoulder syndrome.” Acromioclavicular arthritis is not as frequent or as disabling as the other manifestations of this disease.

Examination of lower extremities

Ankles and feet

The ankle joint itself is rarely involved without midfoot or MTP involvement. Because it is a mortise joint, it does not often deform. Major structural changes occur in the midfoot and foot as a result of the combination of chronic synovitis and weight bearing. Posterior tibialis tendon involvement or rupture may lead to subtalar subluxation, which results in eversion and migration of the talus laterally. Midfoot disease leads to loss of normal arch contour with flattening of the feet.

The MTP joints are inflamed in most patients and, because of the heavy loads they bear, often become deformed over time. The great toe typically develops hallux valgus (a bunion); subluxation of the phalanx at the MTP joint of the other toes predominantly occurs dorsally. Toes may exhibit compensatory flexion due to a fixed length of the flexor tendons—so-called hammer toes. The second and third metatarsal heads commonly protrude and may become the primary weight-bearing surface at the MTP joints. Calluses and pain upon weight bearing result.

Knees

Affected knees may develop large effusions and abundant accumulation of synovium. Knee effusions and synovial thickening are common in RA and are easily detected during the early course of the disease. Persistent effusions may lead to inhibition of quadriceps function by spinal reflexes, resulting in subsequent atrophy.

Instability may develop after progressive loss of cartilage and weakening of ligaments; deformity may include genu valgus or varus, as well as flexion deformities. The patient’s energy expenditure for standing or walking increases substantially if there are flexion deformities of the knees.

Hips

The hips are commonly involved in RA; however, because of their deep location, their involvement is not always readily apparent early in the course of the disease. Hips are difficult to examine by means of direct inspection or palpation.

Limited motion or pain on motion and weight bearing are the hallmarks of hip involvement. The Patrick maneuver (flexion, external rotation, and abduction) is abnormal in this situation. A flexion deformity may be demonstrable by conducting a Thomas test, which is performed by flexing one hip (with the patient supine) while restricting pelvic motion by keeping the other hip in the neutral position on the examination table. If the hip cannot be maintained in the neutral position, a contracture is present.

Cervical spine

Cervical spine involvement (see the following image) usually affects C1-C2 and has the potential to cause serious neurologic consequences. Patients who are to undergo intubation or procedures that may involve manipulation of the neck should undergo careful evaluation of the cervical spine.

Ankylosis in the cervical spine at several levels due to long-standing juvenile rheumatoid arthritis (also known as juvenile idiopathic arthritis).

Neck pain on motion and occipital headache are common manifestations of cervical spine involvement. Most patients with cervical spine involvement (see the image below) have had the disease for more than 10 years.

Lateral view of the cervical spine in a patient with rheumatoid arthritis shows erosion of the odontoid process.

Clinical manifestations of early cervical spine disease consist primarily of neck stiffness that is perceived throughout the entire arc of motion. The atlantoaxial joint is a synovial-lined joint and is susceptible to the same proliferative synovitis and subsequent instability seen in the peripheral joints. Patients with severe destruction in the hands (arthritis mutilans) are very likely to have symptomatic cervical spine abnormalities, as are those patients taking significant amounts of corticosteroids for control of RA.

Neurologic involvement in the cervical spine ranges from radicular pain to a variety of spinal cord lesions that may result in weakness (including quadriparesis), sphincter dysfunction, sensory deficits, and pathologic reflexes.

Transient ischemic attacks (TIAs) and cerebellar signs may reflect vertebral artery impingement from cervical subluxation or basilar artery impingement from upward migration of the dens. Tenosynovitis of the transverse ligament of C1 may lead to C1-C2 instability. Myelopathy secondary to rupture of the transverse ligament may lead to neurologic deficits. Radiculopathy is most common at the C2 root, though symptomatic subluxations may occur at any level.

Symptoms of cervical myelopathy are gradual in onset and are often unrelated to either the development or the accentuation of neck pain. When neck pain does occur, it frequently radiates over the occipital region in the distribution of the C1-3 nerve roots. The Lhermitte sign, in which tingling paresthesia that descends through the thoracolumbar spine occurs as the cervical spine is flexed, is typically observed.

Stiffness, Tenderness, and Pain on Motion

On physical examination, stiffness in patients with RA is determined by limitation of motion, which may vary with the time of day. However, stiffness that is due to articular surface derangement or soft tissue contractures about the joint does not vary with the time of day.

Severe stiffness in the hands may improve with heat, but it is most effectively relieved with active exercise. These modalities reduce stiffness immediately after application, but unfortunately, they do not prevent the return of stiffness.

Direct palpation can elicit joint tenderness, which can vary significantly among patients and with the method of application of force used. To minimize variation over time, the examiner should try to apply approximately the same pressure for each patient examined.

The enlarged synovial membrane, periarticular ligaments, and supporting structures are the major pain-sensitive structures. Muscles may also become tender, but rarely is this due to myositis. Muscle tenderness is not specific for RA. Severe muscle tenderness should suggest another differential diagnosis, including fibromyalgia or a regional pain disorder (see DDx). Bony prominences are generally tender; periarticular structures tend to be more vulnerable to palpation at these sites.

Pain on motion is often used as a surrogate for tenderness in joints that are not readily amenable to direct palpation because of overlying muscle and other tissues. Such areas include the cervical spine, shoulder, and hip.

Pain on motion of the joint may be due to noninflammatory processes that also interfere with the joint’s normal, almost frictionless motion, including damage of cartilage and bone. Additionally, joint instability or subluxation causes pain on motion because of musculotendinous imbalances across the joint. Documenting the positions of motion at which pain occurs can be useful.

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Swelling, Deformity, and Limitation of Motion

In RA, enlargement of the synovial membrane is noted on physical examination as thickening of the synovium that may obscure joint margins. This thickening is most evident in the small joints of the hands and feet. In the MCP and MTP joints, the outline of the base of the proximal phalanx may become indistinct, and in the PIP joints of the fingers, a fusiform swelling is noted that is due to the anatomy of the synovial reflections (see the image below).

Soft-tissue swelling and early erosions in the proximal interphalangeal joints in a patient with rheumatoid arthritis of the hands.

If synovial proliferation is abundant, the resultant soft-tissue mass may have a doughy texture on palpation. Such synovial proliferation is commonly identified in the PIP, MCP, elbow, ankle, MTP, and knee joints, as well as in the flexor tendons of the fingers, the common extensor compartment of the dorsal wrist, and the extensor carpi ulnaris tendon sheath.

Joint effusions may also contribute to swelling by distending the joint. When the effusion is put under increased pressure with joint flexion, the synovium may be forced between articular structures, with the result that a portion becomes trapped and separated from the rest of the joint, forming a Baker cyst (see the image below). More fluid is forced into the structure with subsequent loading of the distended joint, and a 1-way valve effect may prevent the fluid from returning to the joint.

Anteroposterior radiograph of the knee shows uniform joint-space loss in the medial and lateral knee compartments without osteophytosis. A Baker cyst is seen medially (arrowhead).

Baker cysts may be seen in most peripheral joints and are most commonly recognized in the knee.
[35] The larger the effusion, the more likely it is that a painful cyst will develop in the popliteal fossa. Rupture of a Baker cyst at the knee may resemble acute thrombophlebitis, with distal dissection of inflammatory joint contents along fascial planes as far as the ankle and dorsal foot.

Deformity of the joint may develop over time as articular and supporting structures are damaged by the inflammatory process. By the time deformity has developed, the diagnosis of RA is in little doubt; however, optimal management of RA requires that the inflammatory aspects of the arthritis be recognized before the development of deformity.

Loss of cartilage from proteolytic and mechanical degradation, combined with stretching and weakening of the periarticular ligaments and their attachments, allows forces acting across the joints to deform them. The small joints in the hands and feet are most commonly deformed in this manner; more than 10% of patients with RA develop deformity of the small joints of the hands within the first 2 years of the disease, and at least 33% develop such deformities over time. Joint instability is seen if disruption of supporting structures has occurred.

Limitation of motion occurs as a result of articular surface damage, joint and tendon sheath swelling, or alteration of joint supporting structures. Effusion may limit joint motion through pain or by causing sufficient tightness of the joint capsule to impede joint mobility. Fibrosis involving tendons and muscles may limit normal joint motion and result in flexion contractures. Joint deformities and subluxations invariably limit motion because of mechanical factors.

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Extra-articular Manifestations

RA is a systemic disease, and most individuals with this condition experience extra-articular manifestations such as generalized malaise and fatigue. Rarely, a patient presents with extra-articular manifestations before the onset of arthritis. Some of these manifestations are more common in men (eg, pleural involvement, vasculitis, and pericarditis), but overall, the sex distribution of extra-articular manifestations of the disease is similar to that of RA.

Rheumatoid nodules

Rheumatoid nodules occur in approximately 25% of patients with RA, but they occur in fewer than 10% of patients during the first year of the disease. These lesions are most commonly found on extensor surfaces or sites of frequent mechanical irritation.

The olecranon process, the proximal ulna, the back of the heel, the occiput, and the ischial tuberosities are common periosteal sites for rheumatoid nodule development. Nodules may also form in subcutaneous tissues of the fingers, in toe and heel pads, in tendons, and in viscera. Rheumatoid factor (RF) is almost invariably present in patients with rheumatoid nodules; the absence of RF suggests other diagnoses.

Frequently, there is a discrepancy between the level of articular inflammation and the progression of nodule formation. Patients with rheumatoid nodulosis have a great number of nodules, usually subcutaneous, and may have little active synovitis. In a similar fashion, patients whose articular inflammation responds well to treatment with methotrexate (MTX) may have a seemingly paradoxical rapid increase in the number of nodules.

RA involvement of the lungs may take several forms, including pleural effusions, interstitial fibrosis, nodules, and bronchiolitis obliterans organizing pneumonia. Methotrexate therapy can induce interstitial fibrosis that may be difficult to distinguish from that which naturally occurs in patients with RA.

The kidneys usually are not directly affected by RA. Secondary involvement is common, including that due to medications (eg, nonsteroidal anti-inflammatory drugs [NSAIDs], gold, and cyclosporine), inflammation (eg, amyloidosis), and associated diseases (eg, Sjögren syndrome with renal tubular abnormalities).

GI involvement, like renal involvement, is often secondary to associated processes such as medication effects, inflammation, and other diseases. The liver may be affected in patients with Felty syndrome (ie, RA, splenomegaly, and neutropenia).

Vasculitic lesions can occur in any organ, but they are most commonly found in the skin. Lesions may present as palpable purpura, skin ulcers, or digital infarcts.

Some patients with active RA have an anemia of chronic disease. Several hematologic parameters parallel disease activity, including normochromic-normocytic anemia, thrombocytosis, and eosinophilia, though the last of these is uncommon. Leukopenia is a finding in patients with Felty syndrome.

Nerve entrapment is common, as with the median nerve in carpal tunnel syndrome. Vasculitic lesions, mononeuritis multiplex, and cervical myelopathy may cause serious neurologic consequences. Peripheral myopathy may be noted as well.

Keratoconjunctivitis sicca is common in individuals with RA, and this condition is often the initial manifestation of secondary Sjögren syndrome. The eye may also have episcleritis, uveitis, and nodular scleritis that may lead to scleromalacia.

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2010 ACR/EULAR Diagnostic Criteria

Historically, the diagnosis of RA was based on the 1987 American College of Rheumatology (ACR) criteria. These criteria were based on the persistence of arthritic symptoms over time; however, this classification system failed to identify patients with early inflammatory arthritis.

It is now recognized that early therapeutic intervention significantly improves clinical outcomes and reduces irreversible joint damage and disability. With this focus, the ACR and the European League Against Rheumatism (EULAR) devised new classification criteria for early arthritis, which assess joint involvement, autoantibody status, acute-phase response, and symptom duration, as well as revised criteria for classifying RA in newly presenting patients, those with erosive disease typical of RA, and those with inactive disease with or without treatment.
[36]

Classification of RA

The 2010 ACR/EULAR classification criteria for RA are designed to identify patients with unexplained inflammatory arthritis in at least 1 peripheral joint and a short duration of symptoms who would benefit from early therapeutic intervention. They represents a paradigm shift from the 1987 ACR criteria, which lacked the sensitivity to detect early RA.
[1]

According to the ACR/EULAR criteria, patients who should be tested are those (1) who have at least 1 joint with definite clinical synovitis and (2) whose synovitis is not better explained by another disease (eg, lupus, psoriatic arthritis, or gout).

The ACR/EULAR classification system is a score-based algorithm for RA that incorporates the following 4 factors:

Joint involvement

Serology test results

Acute-phase reactant test results

Patient self-reporting of the duration of signs and symptoms

The maximum number of points possible is 10. A classification of definitive RA requires a score of 6/10 or higher. Patients with a score lower than 6/10 should be reassessed over time. If patients already have erosive changes characteristic of RA, they meet the definition of RA, and application of this diagnostic algorithm is unnecessary.

Joint involvement consists of swelling or tenderness upon examination. The presence of synovitis may be confirmed on imaging studies. Points are allocated as follows:

1 large joint (ie, shoulders, elbows, hips, knees, ankles) = 0 points

2-10 large joints = 1 point

1-3 small joints (with or without involvement of large joints), such as MCP, PIP, second to fifth MTP, thumb interphalangeal (IP), and wrist joints = 2 points

4-10 small joints (with or without involvement of large joints) = 3 points

More than 10 joints (at least 1 small joint, plus any combination of large and additional small joints or joints such as the temporomandibular, acromioclavicular, or sternoclavicular) = 5 points

At least 1 serology test result is needed for RA classification. Points are allocated as follows:

Negative serology test results are defined as international unit (IU) values that do not exceed the upper limit of normal (ULN) for the reporting laboratory or assay. Low-positive results are defined as IU values that exceed the ULN but are no more than 3 times the ULN for the reporting laboratory or assay. High-positive results are IU values that are more than 3 times higher than the ULN for the reporting laboratory or assay. When RF is available only as a positive or negative finding, a positive result should be scored as low-positive RF.

At least 1 test acute-phase reactant test result is needed for classification. Local laboratory standards determine which results are normal and which are abnormal. Points are allocated as follows:

Points for the patient’s self-reporting of the duration of signs or symptoms of synovitis in clinically involved joints are allocated as follows:

Shorter than 6 weeks = 0 points

6 weeks or longer = 1 point

A 2014 systematic literature review by Radner et al concluded that the 2010 ACR/EULAR criteria have a pooled sensitivity for RA of 0.82 (95% confidence index [CI], 0.79-0.84) and a specificity of 0.61 (95% CI, 0.59-0.64). These authors' review of research that directly compared the 2010 ACR/EULAR criteria with 1987 ACR criteria found that the ACR/EULAR criteria had higher overall sensitivity (+0.11 compared with 1987 criteria) at the cost of lower overall specificity (-0.04).
[37]

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2012 ACR Disease Activity Measures

In April 2012, the ACR published new recommendations for the measurement of disease activity for clinical use at the point of care. The scales used included the following 6 recommended measures
[2] :

The 6 measures above result in a single continuous index with defined ranges for low, moderate, or high disease activity or clinical remission.
[2] In addition, the data collected from these measures are not solely dependent on the patient’s report, the clinician’s assessment, or laboratory measurements.

For the CDAI patient and provider composite tool (scale, 0-76), low/minimal disease is in the range of greater than 2.8 to 10.00; moderate disease, greater than 10.0 to 22.0; and high/severe disease, greater than 22.0.
[2]

The following disease activity cutoffs are for the ACR-recommended RA patient, provider, and laboratory composite tools
[2] :

DAS28 (ESR or CRP) (scale, 0-9.4) – Low/minimal disease, 2.6 or more to less than 3.2; moderate disease, 3.2 or more to 5.1 or less; high/severe disease greater than 5.1

Measurement of disease remission

In 2011, the ACR and the EULAR published a Boolean-based definition of remission in RA, according to which a patient must satisfy all of the following to be considered in remission
[3] :

Tender joint count of 1 or less (if joints are tender and swollen, a 28-joint count may miss actively involved joints, particularly those in the feet and ankles; include the feet and ankles when assessing for remission)

Swollen joint count of 1 or less (as noted above, include the feet and ankles when assessing for remission)

In addition, the ACR/EULAR index-based definition considers RA patients to be in remission if they have an SDAI score of 3.3 or lower. The SDAI score is defined as the sum of the tender joint count (28 joints), swollen joint count (28 joints), patient global assessment (0-10 scale), and CRP measurement (mg/dL).
[3]

Given the cost and potential adverse effects of newer drugs used to treat RA, individualized treatment requires knowledge of poor prognostic factors. A systematic review of prospective studies identified 16 independent clinical, laboratory, and genetic factors predictive of RA remission. Although the predictive value of these factors remains to be confirmed, early aggressive treatment has been shown to improve outcomes regardless of poor prognostic factors.
[38]

Complications

RA itself is not fatal, but complications of the disease may shorten survival by years in some individuals. In general, RA is progressive and cannot be cured, but in some patients, the disease gradually becomes less aggressive, and symptoms may even improve. However, if bone and ligament destruction and any deformities have occurred, the effects are permanent.

Joint disability and pain with daily life are common. Affected joints can become deformed, and the performance of even ordinary tasks may be very difficult or impossible; these factors can severely affect patients’ quality of life. In addition, RA is a systemic disease that can affect other parts of the body in addition to joints. These effects include the following:

Anemia

Infections – Patients with RA are at greater risk for infections; immunosuppressive drugs further increase that risk

GI problems – Patients with RA may experience stomach and intestinal distress; however, lower rates of stomach and colorectal cancers have been reported in RA patients

Osteoporosis – This condition is more common than average in postmenopausal women with RA; the hip is particularly affected; the risk of osteoporosis appears to be higher than average in men with RA who are older than 60 years

Lung disease – A small study found a high prevalence of pulmonary inflammation and fibrosis in patients with newly diagnosed RA, but this finding may be associated with smoking

Ankylosis in the cervical spine at several levels due to long-standing juvenile rheumatoid arthritis (also known as juvenile idiopathic arthritis).

Widespread osteopenia, carpal crowding (due to cartilage loss), and several erosions affecting the carpal bones and metacarpal heads in particular in a child with advanced juvenile rheumatoid arthritis (also known as juvenile idiopathic arthritis).

Rheumatoid changes in the hand. Photograph by David Effron MD, FACEP.

Rheumatoid nodules at the elbow. Photograph by David Effron MD, FACEP.

Soft-tissue swelling and early erosions in the proximal interphalangeal joints in a patient with rheumatoid arthritis of the hands.

Subluxation in the metacarpophalangeal joints, with ulnar deviation, in a patient with rheumatoid arthritis of the hands.

Coronal, T1-weighted magnetic resonance imaging scan shows characteristic pannus and erosive changes in the wrist in a patient with active rheumatoid arthritis. Courtesy of J. Tehranzadeh, MD, University of California at Irvine.

Lateral view of the cervical spine in a patient with rheumatoid arthritis shows erosion of the odontoid process.

Boutonniere deformity.

Anteroposterior radiograph of the knee shows uniform joint-space loss in the medial and lateral knee compartments without osteophytosis. A Baker cyst is seen medially (arrowhead).

Ultrasonography-guided synovial biopsy of the second metacarpophalangeal joint of the right hand in a patient with rheumatoid arthritis of the hands. The biopsy needle is seen as a straight echogenic line on the left side of the image in an oblique orientation.

Lateral view of the cervical spine in a patient with rheumatoid arthritis shows erosion of the odontoid process.

T1-weighted sagittal magnetic resonance image of the cervical spine shows basilar invagination with cranial migration of an eroded odontoid peg. There is minimal pannus. The tip of the peg indents the medulla, and there is narrowing of the foramen magnum due to the presence of the peg. Inflammatory fusion of several cervical vertebral bodies is shown.

Sagittal T2-weighted magnetic resonance image of cervical spine in same patient as in previous image. Compromised foramen magnum is easily appreciated, and there is increased signal intensity within upper cord; this is consistent with compressive myelomalacia. Further narrowing of canal is seen at multiple levels.

Lateral radiograph of the same patient as in Images 4-5. Midcervical vertebral-body fusions are shown. The eroded peg is difficult to visualize, but inferior subluxation of the anterior arch of C1 is shown.

Lateral radiograph of a normal cervical spine shows the McGregor line. The odontoid tip should not protrude more than 4.5 mm above the line, which is drawn from the posterior edge of the hard palate to the most caudal point of the occiput.

Normal lateral magnified radiograph of the cervical spine shows the Ranawat method of detection of cranial settling. This method is used to measure the distance from the center of the pedicles (sclerotic ring) of C2 to a line drawn connecting the midpoints of the anterior and posterior arches of C1. (Normal values are 15 mm or greater for males and 13 mm or greater for females.)

Lateral radiograph of the cervical spine shows how the cervical height index (CHI) is calculated. The distance from the center of the sclerotic ring of C2 to the tip of the spinous process of C2 (dotted line) is measured. This is then divided into the distance from the center of the sclerotic ring of C2 to the midpoint of the inferior border of the body of C7. A CHI of less than 2 mm is a sensitive predictor of neurologic deficit.

X-ray shows total hip replacement, with prosthesis, in patient with osteoarthritis.

This gross photo shows destruction of the cartilage and erosion of the underlying bone with pannus from a patient with rheumatoid arthritis.

The hallmark of rheumatoid arthritis is a perivascular mononuclear cell infiltrate in the synovium (pictured here). The early stages are noted to have plasma cells as well, and syphilis needs to be part of the differential diagnosis.

The inflammation involved in rheumatoid arthritis can be intense. It is composed of mononuclear cells and can resemble a pseudosarcoma.

A 72-year-old man with long-standing rheumatoid arthritis (RA) developed blue-grayish discoloration of his skin. He had been on hydroxychloroquine for approximately 15 years. The diagnosis was hydroxychloroquine-related hyperpigmentation. Image courtesy of Jason Kolfenbach, MD, and Kevin Deane, MD, Division of Rheumatology, University of Colorado Denver School of Medicine.

A 64-year-old woman with rheumatoid arthritis has developed nodules on the dorsal and volar aspect of her fingers, as well as the posterior aspect of her heels. The diagnosis is RA nodules with methotrexate-induced accelerated nodulosis. Image courtesy of Jason Kolfenbach, MD, and Kevin Deane, MD, Division of Rheumatology, University of Colorado Denver School of Medicine.

A 64-year-old woman with rheumatoid arthritis has developed nodules on the dorsal and volar aspect of her fingers, as well as the posterior aspect of her heels. The diagnosis is RA nodules with methotrexate-induced accelerated nodulosis. Image courtesy of Jason Kolfenbach, MD, and Kevin Deane, MD, Division of Rheumatology, University of Colorado Denver School of Medicine.

If disease activity remains moderate or high despite DMARD monotherapy, ACR guidelines recommend one of the following:

Combination DMARDs

Add an anti-TNF biologic

Non-TNF biologic

Tofacitinib

If disease activity remains moderate or high despite use of a single anti-TNF biologic:

Switch to a non-TNF biologic with or without MTX over another anti-TNFi or Tofacitinib

If disease activity remains moderate or high despite use of one anti-TNF biologic and one non-TNF biologic:

Use another non-TNF biologic with or without MTX over Tofacitinib

If still uncontrolled use Tofacitinib

(Notable change from 2012 to 2015 guidelines: Instead of switching from one anti-TNF biologic to another anti-TNF biologic because of continued activity, it is recommended to change first to a non-TNF biologic)

If the chest x-ray is suspicious for active TB, obtain sputum examination for active disease

Negative

In patients with RA but without risk factors or clinical suspicion for TB

No further workup is needed

In patients with RA and immunosuppression plus LTBI risk factors

LBTI is not excluded

Repeat the TST or IGRA 1-3 wk after an initial negative test result

Active/latent TB

Treat with appropriate antitubercular therapy

Refer to a specialist as necessary

Initiate or resume biologic agents after either 1 mo of treatment of LTBI with antitubercular regimen or completion of treatment for active TB

Screen annually in individuals with RA who (1) are continuing on biologic agents while living, traveling, or working in situations of likely TB exposure and (2) have a positive baseline for TST or IGRA; TST or IGRA may still be positive after successful TB therapy; monitor for clinical signs or symptoms of recurrent TB

Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Patrick M Foye, MD Associate Professor of Physical Medicine and Rehabilitation, Co-Director of Musculoskeletal Fellowship, Co-Director of Back Pain Clinic, Director of Coccyx Pain Service (Tailbone Pain Service: www.TailboneDoctor.com), University of Medicine and Dentistry of New Jersey, New Jersey Medical School

Kristine M Lohr, MD, MS Professor, Department of Internal Medicine, Center for the Advancement of Women's Health and Division of Rheumatology, Director, Rheumatology Training Program, University of Kentucky College of Medicine

Robert J Nowinski, DO Clinical Assistant Professor of Orthopaedic Surgery, Ohio State University College of Medicine and Public Health, Ohio University College of Osteopathic Medicine; Private Practice, Orthopedic and Neurological Consultants, Inc, Columbus, Ohio